Spray drying involves atomization of a liquid, such as a solution, suspension or emulsion, for example by spraying through a spray nozzle while contacting with an atomizing gas to form spray particles; by two-fluid nozzle atomization, wherein spray is created by combination of a liquid flow and a gas flow, in which the atomization energy is provided by the gas flow; or by centrifugal atomization, wherein the solution is delivered in a rotating disc, such that spray is created by the energy created by the rotation of the disc. Alternatively, the liquid flow may be sprayed using a pressure nozzle in which the liquid flow is forced through a small aperture, the change in pressure transforming the liquid flow into spray of small droplets.
Formation of spray particles is followed by drying of the spray in a hot gas (e.g. air) flow provided by a drying gas conduit. The spray particles rapidly dry yielding a powder, which is then separated from the hot air flow in a cyclone device, and may be subsequently collected in a collection container, such as a vial. An example of a commercially available spray-drying apparatus 10 is illustrated in FIG. 1, comprising a drying column 12, having a spray nozzle 14 and a drying gas conduit 16.
Spray nozzle 14 has a proximal end 18 and a distal end 20, with a spray nozzle tip 22 at distal end 20. An atomizing component 25 (shown in FIG. 2, which is an enlarged view of spray nozzle 14) is provided at distal end 20 of spray nozzle tip 22, which is responsible for producing a spray from the liquid.
A liquid conduit 24, having a distal end at spray nozzle tip 22, is provided for carrying a liquid to be spray-dried to spray nozzle tip 22, through which the liquid is passed.
FIG. 2 shows a spray nozzle 14 comprising an atomizing component 25. An atomizer gas conduit 26 is provided for guiding an atomizing gas to atomizing component 25, which delivers the atomizing gas to the proximity of distal end of liquid conduit 24 at spray nozzle tip 22. The atomizing gas contacts the liquid during passing or exiting of the liquid out through spray nozzle tip 22, whereby a spray is formed from the liquid. Any suitable inert gas may be used as an atomizing gas including air, nitrogen and argon. Preferably, the atomizing gas is dry, having a relative humidity of no more than about 30%. Typically, the drying gas is heated to a temperature in the range of from about 100° C. to about 190° C.
Drying gas conduit 16 comprises a drying gas outlet 28 for providing a drying gas to dry the spray formed from the liquid upon exiting nozzle tip 22, thereby forming a powder.
The powder produced is separated from the drying gas by a cyclone unit 30, and is collected at the bottom of cyclone unit 30 e.g. in a collection container 32. The paths of the separated drying gas and of the powder are shown in FIG. 1 as 35 and 36, respectively.
As is known, proteins (e.g. fibrinogen) are generally sensitive to high temperature for example, human proteins are sensitive to temperatures of 45° C. or above. As a result, when a protein-containing liquid is spray dried, the resulting spray-dried protein may undergo denaturation and/or reduction or loss of potency. Also, sedimentation at the spray nozzle tip may occur, resulting in partial or full blockage of the spray nozzle tip, loss of material and/or protein aggregation.
In an attempt to reduce the temperature of liquid to be spray-dried in liquid conduit 24, it is known in the art to provide a heat exchange mechanism. One such mechanism is schematically depicted in FIG. 2, comprising two tubes for circulating cool water i.e. a first tube 34a for entry of cool water, arranged concentrically around liquid conduit 24, and a second tube 34b for exit of cool water, with cool water circulating into first tube 34a and out of second tube 34b to a water bath, using a circulation pump (not shown).
Background art include U.S. Pat. No. 5,227,017, U.S. Pat. No. 2,833,345, WO2014078694A1, U.S. Pat. No. 5,851,575A, EP0979377A1, RU2435118C1, DE202005015411U1 and EP2728288A1.